The combined administration of streptozotocin and nicotinamide (S/N) to mature rats induces the development of two islet cell adenomas: (1) Slow tumors, which contain insulin-, glucagon- and somatostatin-positive cells, and (2) fast tumors, which are composed essentially of insulin-producing cells. While slow tumor tissue releases insulin in a biphasic pattern in response to glucose in vitro, the fast tumor's response to glucose is rapid and monophasic. We propose to study the phasic insulin release patterns of slow and fast tumor tissues in a perfusion system, especially in response to the in vitro addition of adenylate cyclase-phosphodiesterase agents (cAMP, theophylline),the paracrine hormones (glucagon, somatostatin) and neurogenic agents, in order to characterize, and perhaps manipulate, the release patterns of fast and slow tumors. The large amount of adenomatous islet tissue available prompted us to establish an homologous cell-free system for studying the regulation of translation of preproinsulin mRNA. Tumor tissue will be homogenized in liver cell sap and other necessary factors to support protein synthesis, and the whole cells and nuclei will be removed prior to in vitro incubation. The effects of agents which may regulate translation will then be tested on the rate of incorporation of 3H-leucine into insulin-related peptides isolated by gel filtration and electrophoresis. Also, the possibility that tumor insulinase is regulated will be explored by determining the in vitro effects of glucose on the degradation of exogenous insulin, and glutathione-insulin transhydrogenase activity, in tumor tissue homogenates. Finally, the ultrastructure of perfusion-fixed S/N-induced adenomas will be investigated by transmission electron microscopy, especially with regard to cell-cell junctions, innervation, and cell organelle detail.